Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Faculty of Veterinary Medicine, Utrecht University, 3584 CS Utrecht, The Netherlands.
Int J Mol Sci. 2020 Apr 14;21(8):2720. doi: 10.3390/ijms21082720.
Matrix production by nucleus pulposus (NP) cells, the cells residing in the center of the intervertebral disc, can be stimulated by growth factors. Bone morphogenetic proteins (BMPs) hold great promise. Although BMP2 and BMP7 have been used most frequently, other BMPs have also shown potential for NP regeneration. Heterodimers may be more potent than single homodimers, but it is not known whether combinations of homodimers would perform equally well. In this study, we compared BMP2, BMP4, BMP6, and BMP7, their combinations and heterodimers, for regeneration by human NP cells. The BMPs investigated induced variable matrix deposition by NP cells. BMP4 was the most potent, both in the final neotissue glysosaminoglycan content and incorporation efficiency. Heterodimers BMP2/6H and BMP2/7H were more potent than their respective homodimer combinations, but not the BMP4/7H heterodimer. The current results indicate that BMP4 might have a high potential for regeneration of the intervertebral disc. Moreover, the added value of BMP heterodimers over their respective homodimer BMP combinations depends on the BMP combination applied.
核芯细胞（NP）可分泌细胞外基质，核芯细胞位于椎间盘中心。生长因子可刺激 NP 细胞分泌细胞外基质。骨形成蛋白（BMP）极具潜力。尽管 BMP2 和 BMP7 最常被应用，但其他 BMP 也显示出对 NP 再生的潜在作用。异源二聚体可能比同源二聚体更有效，但尚不清楚同源二聚体的组合是否能同样有效。在这项研究中，我们比较了 BMP2、BMP4、BMP6 和 BMP7，及其组合和异源二聚体，以评估它们对人 NP 细胞的再生作用。研究发现，所研究的 BMPs 可诱导 NP 细胞产生不同的细胞外基质沉积。BMP4 的作用最强，无论是在新组织糖胺聚糖含量还是掺入效率方面。BMP2/6H 和 BMP2/7H 异源二聚体比各自的同源二聚体组合更有效，但 BMP4/7H 异源二聚体并非如此。目前的结果表明，BMP4 可能对椎间盘再生具有很高的潜力。此外，BMP 异源二聚体相对于各自的同源二聚体 BMP 组合的附加值取决于应用的 BMP 组合。
